Induction of microsomal prostaglandin E synthase-1 in human gingival fibroblasts

It is well established that prostaglandin E-2 (PGE(2)) plays an important role in inflammatory diseases including periodontitis. Previously we have reported that the inflammatory mediators interleukin-1beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) stimulate PGE(2) synthesis by inducing mRNA expression of cyclooxygenase-2 (COX-2) in human gingival fibroblasts. In present study the involvement of microsomal prostaglandin E synthase-1 (mPGES-1) in relation to PGE2 production was investigated. The results showed that IL-1beta as well as TNFalpha induced mPGES-1 mRNA and protein expression accompanied by enhanced PGE2 production in gingival fibroblasts. The anti-inflammatory steroid dexamethasone (DEX) inhibited mPGES-1 mRNA and protein expression as well as PGE(2) production induced by IL-1beta or TNFalpha. The COX-2 specific inhibitor, celecoxib, in contrast to the nonspecific COX inhibitor, indomethacin, markedly reduced mPGES-1 expression induced by IL-1beta. The results demonstrate that mPGES-1 regulates PGE(2) production in gingival fibroblasts stimulated by inflammatory mediators IL-1beta and TNFalpha. This novel pathway may be a potential target for treatment strategies of periodontal disease.